The preferred haemopoietin receptor of the present invention is referred to herein as “NR2”. The NR2 receptor interacts with leptin and is referred to as a “leptin receptor”. The terms “haemopoietin receptor”, “NR2” and “leptin receptor” are used interchangeably throughout the subject specification. The species from which a particular NR2 is desired is given in single letter abbreviation in lower case before NR2. For example, murine NR2 is “mNR2” and human NR2 is “hNR2”. A recombinant form may have the prefix “r”.
The rapidly increasing sophistication of recombinant DNA techniques is greatly facilitating research into the medical and allied health fields. Cytokine research is of particular importance, especially as these molecules regulate the proliferation, differentiation and function of a wide variety of cells. Administration of recombinant cytokines or regulating cytokine function and/or synthesis is becoming increasingly the focus of medical research into the treatment of a range of disease conditions.
Despite the discovery of a range of cytokines and other secreted regulators of cell function, comparatively few cytokines are directly used or targeted in therapeutic regimums. One reason for this is the pleiotropic nature of many cytokines. For example, interleukin (IL)-11 is a functionally pleiotropic molecule (1,2), initially characterized by its ability to stimulate proliferation of the IL-6-dependent plasmacytoma cell line, T11 65 (3). Other biological actions of IL-11 include induction of multipotential haemopoietin progenitor cell proliferation (4,5,6), enhancement of megakaryocyte and platelet formation (7,8,9,10), stimulation of acute phase protein synthesis (11) and inhibition of adipocyte lipoprotein lipase activity (12, 13). The diverse and pleiotropic function of IL-11 and other haemopoietin cytokines makes these molecules an important group to study, especially at the level of interaction of the cytokines with their receptors. Manipulation and control of cytokine receptors and of cytokine-receptor interaction is potentially very important in many therapeutic situations, especially where the target cytokine is functionally pleiotropic and it is desired to block certain functions of a target cytokine but not all functions.
Another important aspect of cytokine receptors is in the search for new cytokines. In this regard, the inventors have used a procedure for cloning haemopoietin receptors without prior knowledge of their ligands. Identification of receptors then provides a screening procedure for potentially new cytokines and for previously characterised cytokines. In addition, identification of new haemopoietin receptors allows for selective blocking of pleiotropic cytokine function.
In accordance with the present invention, the inventors identified a novel haempoietin receptor which interacts with leptin, a hormone which regulates adipose tissue mass.